Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China.
Department of Biochemistry, College of Basic Medicine, Kunming Medical University, Kunming 650500, China.
Molecules. 2018 Apr 10;23(4):869. doi: 10.3390/molecules23040869.
Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.
阿尔茨海默病（AD）的病理学特征是大脑细胞外空间中β淀粉样蛋白（Aβ）的过度积累。研究表明，Aβ的聚集会引发氧化应激、炎症和神经毒性，导致认知功能障碍。在这项研究中，我们使用脑 Aβ淀粉样变性模型，在体外和体内研究了野黄芩苷的抗淀粉样蛋白形成作用。我们的结果表明，野黄芩苷通过与 Aβ42 结合，有效地抑制寡聚体形成以及原纤维形成，并降低 Aβ寡聚体诱导的 SH-SY5Y 细胞系中的神经毒性。在 APP/PS1 双转基因小鼠中治疗九个月后，野黄芩苷显著改善了行为，降低了大脑和血浆中可溶性和不溶性 Aβ 水平，减少了与 Aβ斑块相关的神经胶质增生和促炎细胞因子 TNF-α 和 IL-6 的水平，减轻了神经炎症，显示出抗淀粉样蛋白形成作用，并强调了干预对 AD 样神经病理学发展或进展的有益影响。
